Tracking HIV Infection & Alcohol Abuse CNS Comorbidity with Neuroimaging - ABSTRACT This application will build on and enable novel extension of our established program of study (R01AA017347), Tracking HIV Infection & Alcohol Abuse CNS Comorbidity with Neuroimaging. The current proposal seeks neural substrates that accelerate brain structural and functional age-related declines in people living with HIV infection (HIV), especially those who meet criteria for Alcohol Use Disorder (AUD). Particular attention is paid to MRI-visible anomalies of white matter hyperintensities (WMH) and non-heme iron deposition that commonly occur in normal aging and may interact with disease. WHM, markers of edematous tissue potentially marking demyelination, are more prevalent among older individuals with HIV infection and even greater in those comorbid with AUD relative to normal aging and may contribute to motor and cognitive deficits. Similarly, non- heme iron deposition in subcortical and cerebellar dentate nuclei increases with age and may underlie disturbance in gait and balance. Whether balance stability and cognitive abilities follow parallel or accelerated aging trajectories in HIV with or without AUD comorbidity and are related to common brain markers remain unclear. Herein, we propose a longitudinal protocol in using a suite of neuroimaging approaches to identify mechanisms of local tissue degradation we hypothesize underpin functional declines in postural stability, gait, and cognition of men and women aging with HIV infection and AUD. Longitudinal study of this population will determine if the brain and behavior deficits are stable or accelerating, i.e., exhibit an age-disease interaction. Specific Aim 1: White Matter Hyperintensity (WMH) volumes, detected with structural MRI using FLuid- Attenuated Inversion Recovery (FLAIR) imaging, will be quantified and distinguished as periventricular (PVWMH) or deep (DWMH) in cortical lobar, brain stem, and arterial regions. Specific Aim 2: Myelin Integrity and Regional Iron Deposition will be measured with Quantitative Susceptibility Mapping (QSM) and Diffusion Tensor Imaging (DTI). Non-heme iron will be quantified as paramagnetic positive susceptibility in subcortical gray matter structures (globus pallidum, caudate, putamen, red nucleus, dentate nucleus ). QSM diamagnetic negative susceptibility in combination with DTI will be used to characterize tissue constituents in white matter tracts and WMH. Specific Aim 3: Static Postural Stability, Dynamic Gait, and Cognition. Static postural stability will be measured with a balance platform yielding metrics of sway path length, sway direction, and truncal tremor. Gait will be video recorded and measured in-house yielding metrics of dynamic gait coherence and stability. Standardized HIV-Associated Neurocognitive Disorder (HAND) composite scores will measure component processes of cognition: executive function, working memory/attention, verbal and visual memory and learning, and spatial abilities. Impact of WMH volume, regional iron deposition, and myelin disruption will be tested with our static and dynamic measures of postural stability and with component processes of cognition.
